title: Evaluation of a multiplex panel of immune-related markers in cervical secretions: a methodologic study.
abstract: Although persistent carcinogenic human papillomavirus (HPV) infection is necessary for cervical carcinogenesis, the cofactors involved in HPV persistence and disease progression are poorly understood. Chronic cervical inflammation may increase risk, but few studies have measured immune markers (cytokines, chemokines and soluble receptors) in cervical secretions. We evaluated the performance of 74 multiplexed, bead-based immune markers in cervical secretions from three groups of women with biopsy evaluation of cervical intraepithelial neoplasia (CIN), (i) <CIN1, HPV-negative (n = 24), (ii) <CIN1, carcinogenic HPV-positive (n = 24) and (iii) CIN2/3, carcinogenic HPV-positive (n = 48), matched on time since last period and smoking status. We considered markers with >25% detectability and >80% interclass correlation coefficients (ICCs) acceptable for epidemiologic studies. Within-batch coefficients of variation (CVs) of ≥25% indicated room for assay improvement. Secondarily, we explored associations between marker levels and CIN/HPV status adjusted for matching variables, assay batch, age and number of sexual partners. Sixty-two markers (84%) had >25% detectability and ICCs > 80%. Of those, 53 (85%) had CVs < 25%. Using these preliminary data, we found that HPV positivity was associated with increased eotaxin-1 [odds ratio (OR): 15.63, 95% confidence interval (CI): 1.26-200.00] and G-CSF (OR: 12.99, 95% CI: 1.10-142.86) among CIN-negative women. There was suggestive evidence that higher chemoattractant marker levels were associated with CIN2/3 (e.g., MIP-1delta, OR: 4.48, 95% CI: 0.87-23.04 versus <CIN1/HPV-positive). More than 70% of markers were reliably measured. This assay may be used to evaluate associations of immune-related markers with CIN and HPV status.
authors.affiliation: Division of Cancer Epidemiology and Genetics, NCI/NIH/DHHS, Bethesda, MD.
authors.forename: Jill
authors.initials: J
authors.lastname: Koshiol
authors.forename: Martha
authors.initials: M
authors.lastname: Sklavos
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Troy
authors.initials: T
authors.lastname: Kemp
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: S Terence
authors.initials: ST
authors.lastname: Dunn
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Zuna
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008163:Luminescent Measurements; D009367:Neoplasm Staging; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism
chemical_list: D015415:Biomarkers
keywords: cervical intraepithelial neoplasia; cervical secretions; human papillomavirus; immunology